6yxa

From Proteopedia

Structure of the bifunctional Rel enzyme from B. subtilis

Structural highlights

6yxa is a 1 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.95Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RELA_BACSU In eubacteria ppGpp (guanosine 3'-diphosphate 5-' diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. This enzyme catalyzes the formation of pppGpp which is then hydrolyzed to form ppGpp, it is probably the hydrolysis activity that is required for optimal growth (Probable).^[1]

Publication Abstract from PubMed

The stringent response enables metabolic adaptation of bacteria under stress conditions and is governed by RelA/SpoT Homolog (RSH)-type enzymes. Long RSH-type enzymes encompass an N-terminal domain (NTD) harboring the second messenger nucleotide (p)ppGpp hydrolase and synthetase activity and a stress-perceiving and regulatory C-terminal domain (CTD). CTD-mediated binding of Rel to stalled ribosomes boosts (p)ppGpp synthesis. However, how the opposing activities of the NTD are controlled in the absence of stress was poorly understood. Here, we demonstrate on the RSH-type protein Rel that the critical regulative elements reside within the TGS (ThrRS, GTPase, and SpoT) subdomain of the CTD, which associates to and represses the synthetase to concomitantly allow for activation of the hydrolase. Furthermore, we show that Rel forms homodimers, which appear to control the interaction with deacylated-tRNA, but not the enzymatic activity of Rel. Collectively, our study provides a detailed molecular view into the mechanism of stringent response repression in the absence of stress.

Structural Basis for Regulation of the Opposing (p)ppGpp Synthetase and Hydrolase within the Stringent Response Orchestrator Rel.,Pausch P, Abdelshahid M, Steinchen W, Schafer H, Gratani FL, Freibert SA, Wolz C, Turgay K, Wilson DN, Bange G Cell Rep. 2020 Sep 15;32(11):108157. doi: 10.1016/j.celrep.2020.108157. PMID:32937119^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nanamiya H, Kasai K, Nozawa A, Yun CS, Narisawa T, Murakami K, Natori Y, Kawamura F, Tozawa Y. Identification and functional analysis of novel (p)ppGpp synthetase genes in Bacillus subtilis. Mol Microbiol. 2008 Jan;67(2):291-304. Epub 2007 Dec 7. PMID:18067544 doi:http://dx.doi.org/10.1111/j.1365-2958.2007.06018.x
↑ Pausch P, Abdelshahid M, Steinchen W, Schafer H, Gratani FL, Freibert SA, Wolz C, Turgay K, Wilson DN, Bange G. Structural Basis for Regulation of the Opposing (p)ppGpp Synthetase and Hydrolase within the Stringent Response Orchestrator Rel. Cell Rep. 2020 Sep 15;32(11):108157. doi: 10.1016/j.celrep.2020.108157. PMID:32937119 doi:http://dx.doi.org/10.1016/j.celrep.2020.108157